The MutS homolog 6 (MSH6) is a nuclear DNA mismatch repair (MMR) gene that encodes the MSH6 protein. MSH6 interacts with MSH2 to form the MutSα heterodimer. MutSα corrects DNA mismatches and unpaired nucleotides arising during DNA replication, deamination of 5-methylcytosine, and recombination between non-identical DNA sequences. In addition to correcting DNA biosynthetic errors, MutSα also recognizes chemically damaged DNA bases. Here, we show that inactivation of MSH6 affects the basal susceptibility of Arabidopsis thaliana to Pseudomonas syringae pv tomato DC3000. The msh6 T-DNA insertional mutant exhibited a reduced susceptibility to the bacterial invasion. This heightened basal resistance of msh6 mutants appears to be dependent on an increased stomatal closure, an accumulation of HO and double-strand breaks (DSBs) and a constitutive expression of pathogenesis-related (NPR1 and PR1) and DNA damage response (RAD51D and SOG1) genes. Complementation of this mutant with the MSH6 wild type allele under the control of its own promoter resulted in reversal of the basal bacterial resistance phenotype and the stomatal closure back to wild type levels. Taken together, these results demonstrate that inactivation of MSH6 increases Arabidopsis basal susceptibility to the bacterial pathogen and suggests a link between DNA repair and stress signaling in plants.
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http://dx.doi.org/10.1016/j.plantsci.2023.111713 | DOI Listing |
Hered Cancer Clin Pract
January 2025
Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Carcinogenesis encompasses processes that lead to increased mutation rates, enhanced cellular division (tumour growth), and invasive growth. Colorectal cancer (CRC) carcinogenesis in carriers of pathogenic APC (path_APC) and pathogenic mismatch repair gene (path_MMR) variants is initiated by a second hit affecting the corresponding wild-type allele. In path_APC carriers, second hits result in the development of multiple adenomas, with CRC typically emerging after an additional 20 years.
View Article and Find Full Text PDFClin Exp Dermatol
January 2025
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Background: One in five sebaceous tumour (ST) patients may have Lynch syndrome (LS), a hereditary cancer predisposition. LS patients benefit from cancer surveillance and prevention programmes and immunotherapy. Whilst universal tumour mismatch repair (MMR) deficiency testing is recommended in colorectal and endometrial cancers to screen for LS, there is no consensus screening strategy for ST, leading to low testing rates and inequity of care.
View Article and Find Full Text PDFSurg Pract Sci
December 2024
Faculty of Medicine University of Tasmania, Tasmania, Australia.
Aims: Medullary carcinoma of the colon is a rare subtype of adenocarcinoma, first described in 1999. Clinically known to have a favourable prognosis in comparison to poorly differentiated cancers, it is associated with deficient mismatch repair. This is an observational single center study of patients with medullary cancer, and comparison with the current literature.
View Article and Find Full Text PDFBMJ Case Rep
January 2025
Department of Respiratory and Critical Care Medicine, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genetic disorder. This case report aims to increase awareness of pulmonary cystic lesions and BHDS in China by providing insights into the clinical features of this syndrome. We present two cases of BHDS from the same family.
View Article and Find Full Text PDFFree Neuropathol
January 2024
NeuroMarkers, Houston, Texas, USA.
Glioblastoma is the most frequent and malignant primary brain tumor. Although the survival is generally dismal for glioblastoma patients, risk stratification and the identification of high-risk subgroups is important for prompt and aggressive management. The G1-G7 molecular subgroup classification based on the MAPK pathway activation has offered for the first time a non-redundant, all-inclusive classification of adult glioblastoma.
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